Baroreflexes are an important part of the neural regulation of the cardiovascular system, but the cellular basis of the central nervous system (CNS) contribution to these reflexes is poorly understood. The area of densest innervation by the baroreceptor afferents is in the dorsomedial portion of the nucleus of the tractus solitarius (NTS). Reflex studies and extracellular recordings of neuron activity from the medulla suggest that the NTS is a key area where incoming afferent information is transformed before going on to other brain areas involved in the control of heart rate and blood pressure. A number of studies suggest that the properties of NTS neurons may be altered during hypertension. The proposed work will focus on characterizing the cellular basis of synaptic transmission at the afferent-NTS synapse. CNS studies are hampered by difficulties in gaining physical access to these small neurons and in recording conditions in the intact brain. Thus most of what we know about NTS neurons is based on extracellular activity recordings which provide limited information. An in vitro longitudinal slice preparation of the rat medulla has been developed to study medial NTS neurons using intracellular recordings to measure responses to afferent synaptic input. The longitudinal slice offers important advantages by preserving both lengthy sections of the solitary tract and key anatomical landmarks for microelectrode placement and by providing precise of control experimental conditions such as drug concentrations. Electrical stimulation of afferent axons will be used to evoke postsynaptic responses. Several key issues in afferent-NTS synaptic transmission will be examined including: 1) the mechanism of frequency dependent depression of synaptic responses and the influence of intermittent or burst modes of stimulation, 2) the identity of the primary excitatory transmitter and its postsynaptic receptor type, 3) the potential role and identity of inhibitory transmitters in synaptic modulation, and 4) possible changes in primary excitatory transmission or its modulation in genetic hypertension. Primary candidate neurotransmitters include glutamate, substance P, gamma-aminobutyric acid, and norepinephrine. Dual marking (with transganglionic transport of horseradish peroxidase in aortic baroreceptor nerves and intracellular dye injection) will be used to identify neurons characterized electrophysiologically which received cardiovascular afferent inputs. Immunocytochemistry will identify neurotransmitters localized on cell bodies or processes. These studies should provide important new information concerning the CNS mechanisms involved in a critical step of reflex autonomic control of the hear and blood pressure during normal and pathological states such as hypertension.